Journal: Clinical hemorheology and microcirculation
Substrate stiffness has been proven to play a critical role in vitro tumor proliferation; however, pharmacological studies on antitumor drug screening are still routinely carried out in regular plastic culture plates. In the article, polydimethylsiloxane (PDMS) substrates with different stiffness (mimicking articular cartilage, collagenous bone and mammary tumor respectively) and plastic substrate were employed to establish the mechanical microenvironment for the in vitro drug screening platform. We studied the influences of stiffness on the responses of MCF-7 cells to typical antitumor drugs, cisplatin and taxol. Results showed that for both the treatment IC50 value to MCF-7 cells decreased significantly (p < 0.01) on the rigid substrate, indicating that MCF-7 cells on soft substrate have a resistance to cytotoxicity of antitumor drugs. The sensitivity of MCF-7 cells on rigid substrate to drug cytotoxicity was attributed to the increased cell cycle progression, implying that agents proven to be effective in vitro by conventional screening approach might be inefficient in a soft microenvironment in vivo. We conclude that stiffness of the substrates, as a critical mechanical factor, should be concerned for screening antitumor agents in vitro. As an extrapolation, the extensively used drug screening system needs to be revalued and redesigned.
We assessed the cutaneous microcirculatory reactivity of a clinically unaffected skin region in patients with systemic sclerosis (SSc) compared to healthy controls by measuring transcutaneous oxygen saturation (TcPO2) and Laser Doppler flowmetry (LDF). Twelve consecutive patients with SSc and twelve healthy controls were subjected to TcPO2 monitoring and LDF during cuff-induced ischemia and reactive hyperemia in order to measure the skin oxygen tension and the microcirculatory blood flow. Mean minimal and maximal values of oxygen tension and blood flow, time to peak (TTP), and declining slopes after peaking (slope) were compared between patients with SSc and controls. Compared to the controls, TcPO2 values in SSc were similar during ischemia and diminished during reactive hyperemia, with shorter TTP, and a slower return to baseline (-60% vs. -58%, p = 1.000, +76% vs. +210%, p = 0.047, 137 s vs. 108 s, p = 0.028, -0.009%/s vs. -0.019%/s, p = 0.021, respectively). LDF values, however, did not differ significantly between patients with SSc and controls. Unaffected skin regions of SSc patients showed a significantly diminished postischemic vasodilatory reactivity when assessed by TcPO2 monitoring, but not by LDF, indicating that vasculopathy may represent an early mechanism in the onset of skin sclerosis. TcPO2 measurement may help to detect changes in the microcirculation in SSc with no skin affection.
Since Landsteiner’s discovery of ABO blood groups, RBC agglutination has been one of the most important immunohematologic techniques for ABO and RhD blood groupings. The conventional RBC agglutination grading system for RhD blood typings relies on macroscopic reading, followed by the assignment of a grade ranging from (-) to (4+) to the degree of red blood cells clumping. However, with the new scoring method introduced in this report, microscopically captured cell images of agglutinated RBCs, placed in a microchannel chip, are used for analysis. Indeed, the cell images' pixel number first allows the differentiation of agglutinated and non-agglutinated red blood cells. Finally, the ratio of agglutinated RBCs per total RBC counts (CRAT) from 90 captured images is then calculated. During the trial, it was observed that the agglutinated group’s CRAT was significantly higher (3.77-0.003) than that of the normal control (0). Based on these facts, it was established that the microchannel method was more suitable for the discrimination between agglutinated RBCs and non-agglutinated RhD negative, and thus more reliable for the grading of RBCs agglutination than the conventional method.
Post-occlusive reactive hyperaemia (PORH) and vasodilation induced by acetylcholine (ACh) iontophoresis are tests of endothelial function that can be studied with laser speckle contrast imaging (LSCI). LSCI has the advantage of having good temporal and spatial resolutions but can lead to a high amount of data when several minutes of recordings are needed. Parameters of PORH and ACh iontophoresis vasodilation are therefore often determined by several observers or by the same observer on different days. Nevertheless, inter- and intra-observer reproducibility for the determination of such parameters has not been studied yet. We analyzed inter-observer and intra-observer reproducibility of baseline, peak and plateau determination for the two microvascular tests. Ten recordings of both PORH and ACh iontophoresis have been analyzed by two blinded trained observers. For peak determination, inter-observer coefficient of variation (CV) was 4.7% and 3.0% for PORH and ACh respectively. Intra-observer reproducibility expressed in CV ranges from 2.4% to 5.4% for PORH-peak and ACh-peak. CVs for peak determination are better than for baseline or plateau determination for both microvascular tests. This suggests that when microvascular vasodilations are reported, the data segments measured have to be noted. Finally microvascular tests using LSCI have an excellent intra- and inter-observer reproducibility.
Destruction of the insulin-producing beta cells in type 1 diabetes (T1D) is induced by invasion of immune cells causing pancreatic inflammation. Cannabidiol (CBD), a phytocannabinoid, derived from the plant, Cannabis sativa, was shown to lower the incidence of diabetes in non-obese diabetic (NOD) mice, an animal model of spontaneous T1D development.
This study aims to study the effect of Rho kinase inhibitor fasudil on the expression endothelin-1 (ET-1) and nitric oxide (NO) in rats with hypoxic pulmonary hypertension (HPH).
To assess the performance of conventional high frequency ultrasound (US) and US elastography in diagnosis of complex cystic and solid breast lesions.
Intracellular calcium overload has been implicated in various pathological conditions including ischemia reperfusion injury. This study aims to explore the effect and probable mechanism of dantrolene, a ryanodine receptor and intracellular calcium antagonist, on the skeletal muscle ischemia reperfusion injury.
There is an urgent need to improve the early diagnosis of breast cancer.
Viscosity measurement is challenging due to the internal properties of blood and the artifacts deriving from the various viscometer systems.